High mobility group box 1 (HMGB1) is a nonhistone chromatin protein predominantly located in the nucleus. However, under pathological conditions, HMGB1 can translocate from the nucleus to the cytoplasm and subsequently be released into the extracellular space through both active secretion and passive release mechanisms. The distinct cellular locations of HMGB1 facilitate its interaction with various endogenous and exogenous factors, allowing it to perform diverse functions across a range of diseases. This Perspective provides a comprehensive overview of the structure, release mechanisms, and multifaceted roles of HMGB1 in disease contexts. Furthermore, it introduces the development of both small molecule and macromolecule inhibitors targeting HMGB1 and its interaction with receptors. A detailed analysis of the predicted pockets is also presented, aiming to establish a foundation for the future design and development of HMGB1 inhibitors.

中文翻译：

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靶向 HMGB1 及其与受体的相互作用：挑战和未来方向


高迁移率组 box 1 （HMGB1） 是一种主要位于细胞核中的非组蛋白染色质蛋白。然而，在病理条件下，HMGB1 可以从细胞核转移到细胞质，随后通过主动分泌和被动释放机制释放到细胞外空间。HMGB1 独特的细胞位置促进了其与各种内源性和外源性因子的相互作用，使其能够在一系列疾病中发挥多种功能。本观点全面概述了 HMGB1 在疾病环境中的结构、释放机制和多方面作用。此外，它还介绍了靶向 HMGB1 的小分子和大分子抑制剂的开发及其与受体的相互作用。还对预测的口袋进行了详细分析，旨在为 HMGB1 抑制剂的未来设计和开发奠定基础。